In the last decade, intensive pharmacological research concerning .gamma.-aminobutyric acid (hereinafter designated GABA), a neurotransmittcr in the central nervous system, has taken place.
Increased GABA'ergic activity is useful in the treatment of anxiety, epilepsy and muscular and movement disorders. Furthermore, these compounds can be used as sedatives.
In U.S. Pat. Nos. 4,383,999 and 4,514,414 (Smithkline Beckman Corporation) some derivatives of N-(4-phenylbuten-3-yl)azaheterocyclic carboxylic acids which have, furthermore, inter alia, phenyl, 4-fluorophenyl, cyclohexyl or thienyl in the 4-position, are described. It is stated therein that the compounds are useful as inhibitors of GABA uptake.
According to J. Pharm. Exp. Therap., 228 (1984), 109 et seq., N-(4,4-diphenyl-3-butenyl)nipecotic acid (designated SK&F 89976A). N-(4,4-diphenyl-3-butenyl)guvacine (designated SK&F 100330A), N-(4,4-diphenyl-3-butenyl)-.beta.-homoproline (designated SK&F 100561) and N-(4-phenyl-4-(2-thienyl)-3-butenyl)nipecotic acid (designated SK&F 100604J) are active inhibitors of GABA uptake.
It is further well recognized in the art that .beta.-homoproline, nipecotic acid and guvacine are biological equivalents, at least as far as their GABA-like effects regards. See for example Progress in Medicinal Chemistry 21, 67-120 (1985); ed. Ellis West; Elsevier Science Publishers; Molecular and Cellular Biochemistry 31, 105-121 (1980), and J. Pharm. Exp. Therap., 228 (1984), 109 et seq. In practice of this invention they have been found to be biological equivalents.